CENTRAL ASIAN JOURNAL OF MEDICAL AND NATURAL SCIENCES

Volume: 04 Issue: 03 | May-Jun 2023 ISSN: 2660-4159

http://cajmns.centralasianstudies.org

Effects of Beta-Adrenoblockers in Patients with Cardiovascular

Disease
1. Rakhmatova Iroda Bakhtiyorovna Abstract: The article presents a review of literature data
2. Akmuratova Leyla Shavkatovna and current clinical guidelines on the use of beta-
adrenoblockers in the complex therapy of cardiovascular
diseases at different stages of cardiovascular continuum.
Received 2nd Mar 2023, Key words: beta-adrenoblockers, metoprolol CR/XL,
Accepted 3rd Apr 2023, cardiovascular continuum.
Online 24th May 2023

1,2
Student of 331 group of medical faculty
Samarkand State Medical University

Introduction. Beta-adrenoblockers are the most long used class of cardiovascular drugs and have long
been a major component of pharmacotherapy for almost all stages of cardiovascular continuum, the
first of which in terms of chronology and role in pathogenesis and one of the most important in terms
of primary prevention opportunities of the whole set of cardiovascular events is arterial hypertension
(AH). Moreover, it is the example of AH, paradoxically, that can demonstrate both the evolution of
views on the class of drugs as a whole and the main benefits of its individual members that influence
the choice of a particular drug. In general, it can now be considered proven that there are indications
for prescribing beta-blockers for AH and that the use of modern highly selective lipophilic long-acting
beta-blockers such as metoprolol succinate in its delayed-release form cannot be equated with the use
of "old" drugs, especially atenolol. As for contraindications and side-effects, both are not true for the
entire class of beta-blockers and should also be considered when choosing therapy.
The 2013 European guidelines for the treatment of AH retained beta-adrenoblockers as first-line
therapy for uncomplicated AH [1]. This means that experts do not currently deny the use of beta-
adrenoblockers in the initial treatment of AH, especially if there is a clinical indication for it. Such
indications are not clearly formulated in the current guidelines; the decision on the choice of therapy is
left to the treating physician. However, it is known that beta-adrenoblockers are more effective in
young people with signs of hyperactivity of the sympathetic nervous system - the so-called
hyperkinetic type of circulation. Given the ability of beta-adrenoblockers to reduce plasma renin
activity, they are also more effective in the high-renin forms of AH. Despite the fact that in persons
with metabolic risk factors, especially those with metabolic syndrome, other groups of drugs are now
taking precedence, this category of patients also often has signs of sympathetic nervous system
hyperactivity, primarily sinus tachycardia, which also forms the clinical background for prescribing
beta-adrenoblockers. It is in these situations that the choice of a particular drug is particularly

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CAJMNS Volume: 04 Issue: 03 | May-Jun 2023
important, and in this case it should be made in favour of drugs with high selectivity or vasodilator
properties. A number of epidemiological studies - the Framingham, NHANES I and CASS - have
shown a positive correlation between heart rate (HR) and cardiovascular mortality. For example, the
CASS study, which included a 15-year follow-up of 25 000 patients, analysed the long-term
prognostic value of resting heart rate in relation to the course of coronary heart disease (CHD). It was
convincingly shown that an increase in resting HR has a negative impact on quality of life and life
expectancy. In contrast, a lower resting HR in patients with stable CHD is associated with a lower risk
of cardiovascular complications and mortality. Current national and international guidelines on the
treatment of stable angina pectoris postulate the need to achieve an optimal HR of 50-60 bpm [8]. To
date, beta-adrenoblockers are still the most effective means to reduce HR.
According to the European and Russian guidelines on the treatment of AH, indications for the choice
of beta-adrenoblockers as first-line therapy are a combination of AH with CHD (angina pectoris or
condition after myocardial infarction) and/or chronic heart failure (CHF). Today, this tactic is
absolutely justified due to the unconditional pathogenetic justification and a large evidence base for
the use of beta-adrenoblockers in these categories of patients. Beta-adrenoblockers are the first-line
antianginal therapy in patients with stable CHD, including STEMI. They act directly on the heart and
reduce heart rate, myocardial contractility, atrioventricular conduction and ectopic activity. In
addition, they can increase perfusion of ischaemic areas by prolonging diastole and increasing vascular
resistance and non-ischaemic myocardial areas. Thus, the pathogenetic mechanism of the antianginal
effect of beta-adrenoblockers today does not need additional argumentation, and the positive effect in
relation to secondary prevention of myocardial infarction (MI) has long been turned into the gold
standard of evidence-based medicine. Studies proving the protective effect of beta-adreno-blockers on
the risk of recurrent heart attack and prognosis in general in patients who have had a heart attack have
been published for quite some time, and their results are now rarely cited in the literature. For
example, few people today can accurately reproduce the results of the Stockholm trial of metoprolol in
post-MI patients, in which a total of 301 patients were shown to have an incredible, at the time, 23 %
reduction in overall mortality, 55 % reduction in recurrent MI and 59 % reduction in sudden death
compared to placebo. These days, these data look particularly impressive, as the number of patients in
modern trials is usually in the thousands, and a reduction in overall mortality is very rarely achieved in
their performance. Nevertheless, even this class of drugs, which has such a long and extensive
evidence base, has not escaped attempts to critically rethink its leading place in the secondary
prevention of cardiovascular events. On the one hand, it is recognized that treatment with beta-
adrenoblockers leads to a 30% reduction in the risk of cardiovascular death and a 30% reduction in the
incidence of MI, and that not prescribing beta-adrenoblockers for patients with CHD because of
relative contraindications leads to a more than 3-fold increase in mortality compared with patients
receiving therapy with this group of drugs [5]. However, on the other hand, a recent retrospective
analysis of data from the REACH registry showed that in patients with risk factors for CHD alone,
either a known history of CHD or known CHD without a history of CHD, beta-adrenoblocker use was
not associated with a lower risk of cardiovascular events. The results of this analysis suggest that more
research is needed, particularly in the context of modern cardiovascular disease regimens and the
introduction of other secondary prevention drugs, such as statins and angiotensin converting enzyme
inhibitors (ACEIs), into everyday practice. Research into the use of beta-adrenoblockers in CHF has
also long been classic. Beta-adreno-blockers should be used in all patients with CHF with an ejection
fraction of less than 40%, who have no contraindications for this group of drugs. The rationale for the
use of beta-adrenoblockers in the treatment of CHF is the blockade of the sympathoadrenal system
(SAS), which is in a state of chronic hyperactivation in decompensated patients and determines the
poor prognosis of these patients. The activity of SAS progressively increases in parallel with the
severity of CHF, and from stage II of the disease or functional class (FC II) negative de-adaptive

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properties of catecholamines become predominant. Therefore, the use of beta-adrenoblockers becomes
the most reasonable and effective in patients with clinically significant CHF II-IV class. It has been
proved that hyperactivation of SAS contributes to a significant increase in both the risk of sudden
death and death from decompensation progression. Therefore, the main purpose of beta-
adrenoblockers in the treatment of patients with CHF is to improve prognosis and reduce mortality. It
has now been shown that beta-adrenoblockers have a blocking effect on some other neurohormonal
systems responsible for the progression of CHF - the renin-angiotensin system, the endothelin system
and the cytokine system.
Conclusions: Thus, beta-adrenoblockers in the treatment of CHF are complex neurohormonal
modulators that optimally complement the effects of ACE inhibitors. Recommended drugs for the
treatment of CHF are carvedilol, bisoprolol, slow-release metoprolol succinate, nebivolol. According
to the results of multicentre studies COPERNICUS, CIBIS II, MERIT HF, SENIORS, these drugs are
proven to reduce the rate of overall and cardiac mortality, cases of decompensation of CHF and
repeated hospital admissions for CHF. Suffice it to recall the MEJA1T-OT study [8], in which it was
shown for the first time that adding metoprolol to treatment in patients with CHF and an ejection
fraction reduction of less than 40% leads to a significant improvement in prognosis. The study
included almost 4000 patients who received up to 200 mg per day with stable haemodynamics and was
one of the few studies to be stopped early due to the convincing evidence of a benefit of active therapy
compared to placebo. There was a 38% reduction in cardiovascular mortality, a 49% reduction in CVD
mortality and a 41% reduction in sudden death. At the same time, the MEYT-ET study included
patients with CHF of different etiologies, which makes it fair to recommend the use of metoprolol in
patients with CHF not only associated with CHF. This is also true for patients with AH, who may
develop CHF without overt manifestations of CHD or a history of MI. It is important to remember that
in both CHD and CHF, beta-adrenoblockers are rarely used as monotherapy, but are usually prescribed
in combination with ACE inhibitors or angiotensin II receptor blockers (ARBs) and diuretics. In
congestive CVD, spironolactone is also an important component of therapy, whereas in patients with
angina pectoris, a combination with calcium antagonists (CAs) is often used. However, let us return to
the discussion of the prescription of beta-adrenoblockers in patients with AH. There is another
category of patients for whom they are clearly indicated - those with resistant AH in whom the
combination of renin-angiotensin system blockers with ACs and diuretics is not sufficiently effective.
Indeed, the list of drugs recommended for the treatment of AH includes five classes - ACE inhibitors,
BRAs, diuretics, ACs and beta-adrenoblockers. As the first two groups are combined with each other
very rarely and only for specific indications, if the triple combination fails, beta-adreno-blockers
should be prescribed as a fourth drug if they have not been previously prescribed and the patient has
no absolute contraindications. It should not be assumed that the use of beta-adrenoblockers in the
treatment of resistant AH is of little significance given the relative rarity of this condition. Clinical trial
data.
AH - arterial hypertension, CHF - chronic heart failure, MI - myocardial infarction Unproprietary
name: metoprolol. Dosage form: delayed-release coated tablets. Indications for use.
Arterial hypertension. Angina pectoris. Stable symptomatic chronic heart failure with impaired left
ventricular systolic function (as adjunctive therapy to mainstream treatment of chronic heart failure).
Reduced mortality and recurrent infarction rate after acute myocardial infarction. Cardiac rhythm
disorders, including supraventricular tachycardia, reduced ventricular contraction rate in atrial
fibrillation and ventricular extrasystoles. Functional heart disorders accompanied by tachycardia.
Prevention of migraine attacks. Contraindications. II and III degree atrioventricular block,
decompensated heart failure, permanent or intermittent therapy with inotropic drugs acting on beta-
adrenoreceptors, clinically significant sinus bradycardia, sinus node weakness syndrome, cardiogenic

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CAJMNS Volume: 04 Issue: 03 | May-Jun 2023
shock, severe peripheral circulatory disorders, including at risk of gangrene, arterial hypotension.
Betaloc ZOC is contraindicated in patients with suspected acute myocardial infarction with HR less
than 45 beats per minute, PQ interval greater than 0.24 seconds or systolic blood pressure less than
100 mmHg. Known hypersensitivity to metoprolol and its components or other (J-adrenoblockers.
Intravenous administration of slow calcium channel blockers such as verapamil is contraindicated in
patients receiving (5-adreno-blockers. Under 18 years of age (efficacy and safety have not been
determined). Caution: Degree I atrioventricular blockade, Prinzmetal angina pectoris, bronchial
asthma, chronic obstructive pulmonary disease, diabetes mellitus, severe renal insufficiency, severe
hepatic insufficiency, metabolic acidosis, co-administration with cardiac glycosides. Side effects.
Betaloc ZOC is well tolerated by patients, side effects are generally mild and reversible. To estimate
the frequency of cases the following criteria were applied: very common (>10%), common (1-9.9%),
infrequent (0.1-0.9%), rare (0.01-0.09%) and very rare (<0.01%). Cardiovascular system. Frequent:
bradycardia, orthostatic hypotension (very rarely accompanied by syncope), cold extremities,
palpitations; Infrequent: temporary worsening of heart failure symptoms, AV block of degree I;
cardiogenic shock in patients with acute myocardial infarction, edema, pain in the heart; Rare: other
conduction disorders, arrhythmias; Very rare: gangrene in patients with previous severe peripheral
circulatory disorders.
Central nervous system. Very common: increased fatigue; Frequent: dizziness, headache; Infrequent:
paraesthesia, seizures, depression, decreased concentration, drowsiness or insomnia, nightmares; Rare:
increased nervous excitability, anxiety; Very rare: amnesia/memory disturbances, depression,
hallucinations. Gastrointestinal tract. Often: nausea, abdominal pain, diarrhea, constipation;
Infrequent: vomiting; Rare: dry mouth. Liver. Rare: liver dysfunction; Very rare: hepatitis. Skin.
Infrequent: skin rash (as psoriasis-like urticaria), increased sweating; Rare: hair loss; Very rare:
photosensitization, exacerbation of psoriasis. Respiratory organs. Often: dyspnea on exertion;
Infrequent: bronchospasm; Rare: rhinitis. Sensory organs. Rare: visual disturbances, dry and/or
irritated eyes, conjunctivitis; Very rare: ringing in the ears, disorders of taste. Musculoskeletal system.
Very rare: arthralgia. Metabolism. Infrequent: increase in body weight. Blood. Very rare:
thrombocytopenia. Epidemiological studies have shown that resistance to therapy, i.e. the
ineffectiveness of three or more drugs at adequate doses, is common in 2 to 40% of patients in
specialist departments and in more than 5% of patients with AH in general. Given the high prevalence
of AH, the absolute number of individuals who need to be prescribed beta-adrenoblockers for BP
control alone may be higher than the proportion who have had a MI or have CHF.
A separate group of AH patients for whom beta-adrenoblockers are indicated are those with persistent
atrial fibrillation, in whom beta-adrenoblockers form the basis for reducing ventricular contractions
and are used to reduce BP in the first place. This group is small but clinically significant. Long-acting
drugs are indicated in these patients, e.g. metoprolol, whose dosage form is able to maintain a constant
concentration in the blood, which is essential given the possibility of circadian fluctuations in
atrioventricular conduction velocity. Beta-adrenoblockers, although they are one of the oldest classes
of cardiovascular drugs, still hold a leading position in the treatment of cardiovascular pathology. They
are applicable at almost all stages of the cardiovascular continuum, highly effective and most
commonly prescribed as part of the first-line drugs. For each of the modern beta-adrenoblockers, there
are clinical situations where they are most effective, and metoprolol succinate is the leader in the
number of these situations.
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